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Molecular mechanism of testicular dysfunction induced by titanium dioxide nanoparticles

Research Project

Project/Area Number 15H02829
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionNational Institute of Occupational Safety and Health,Japan

Principal Investigator

Miura Nobuhiko  独立行政法人労働者健康安全機構労働安全衛生総合研究所, 産業毒性・生体影響研究グループ, 部長代理 (20229644)

Co-Investigator(Kenkyū-buntansha) 大谷 勝己  独立行政法人労働者健康安全機構労働安全衛生総合研究所, 産業疫学研究グループ, 統括研究員 (50333373)
吉岡 弘毅  金城学院大学, 薬学部, 助教 (30756606)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords二酸化チタン / ナノ粒子 / 精巣機能 / 精子運動能 / チタンナノ粒子 / IVF法 / 二酸化チタンナノ粒子 / 精巣毒性 / トキシコロジー / 酸化チタン / 肝障害 / 衛生
Outline of Final Research Achievements

We found that titanium dioxide nanoparticles (TiNP) also possess acute testicular dysfunction in addition to subacute testicular dysfunction, since the sperm motility was reduced (by half) after only one day of single administration of TiNP. We also confirmed the decrease in sperm motility in ex vivo experiments in which sperm and TiNP were directly incubated, further, we observed the recuction of the fertility rate by TiNP administration by in vitro fertilization (IVF) assay. These results strongly indicate that TiNP directly attacks not only spermatogonia but also mature spermatozoa present in the cauda epididymis. Although quantitative changes in levels of hormones (testosterone, GnRH, FSH, LH) were not observed by TiNP administration, the results of microarray analysis indicated that TiNP might induce the cytoskeleton disruption by damaging microfilaments and microtubules.

Academic Significance and Societal Importance of the Research Achievements

我々はTiNPの反復曝露で精巣機能障害が生じることを報告してきたが、さらに急性障害も生じ得ること、これは成熟精子への直接的な障害であることを見出した。TiNPの工業的・商業的利用は多い。しかしTiNPのSDSには生殖障害について「情報がないため判断できない」と記載されておりTiNPの生殖影響を把握する必要がある。我々が得た結果は、特にTiNPの原材料を取り扱う男性労働者への精巣機能低下の危険性を示す基盤材料となり、取り扱い時において防護の重要性を促す基礎的知見となる。

Report

(5 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Products Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (13 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [Journal Article] Impairment of fertilization efficiency in mice following nano-sized titanium exposure2019

    • Author(s)
      Nobuhiko Miura, Katsumi Ohtani, Tatsuya Hasegawa, Gi-Wook Hwang, Hiroki Yoshioka
    • Journal Title

      Fund Toxicol Sci

      Volume: 6 Pages: 113-116

    • NAID

      130007649489

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biphasic adverse effect of titanium nanoparticles on testicular function in mice2019

    • Author(s)
      Nobuhiko Miura, Katsumi Ohtani, Tatsuya Hasegawa, Hiroki Yoshioka & Gi-Wook Hwang
    • Journal Title

      Scientific Report

      Volume: 9 Issue: 1 Pages: 14373-14380

    • DOI

      10.1038/s41598-019-50741-9

    • Related Report
      Products Report
    • Open Access
  • [Journal Article] High sensitivity of testicular function to titanium nanoparticles2017

    • Author(s)
      Nobuhiko Miura, Katsumi Ohtani, Tatsuya Hasegawa, Hiroki Yoshioka, Gi-Wook Hwang
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 42 Issue: 3 Pages: 359-366

    • DOI

      10.2131/jts.42.359

    • NAID

      130006865652

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 労働環境におけるナノマテリアルの生体影響2016

    • Author(s)
      三浦伸彦
    • Journal Title

      環境技術

      Volume: 45 Pages: 26-31

    • Related Report
      2016 Annual Research Report
  • [Presentation] 酸化チタンナノ粒子による急性精巣機能障害の誘発機構2019

    • Author(s)
      三浦伸彦,田中廣輝,北條理恵子,大谷勝己,吉岡弘毅
    • Organizer
      第45回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Titanium dioxide nanopaticles-induced testicular dysfunction is mediated by anatase titanium dioxide2019

    • Author(s)
      Hiroki Yoshioka, Nobuhiko Miura
    • Organizer
      フォーラム2018 衛生薬学・環境トキシコロジー 日韓次世代シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 労働衛生と精巣機能障害2018

    • Author(s)
      三浦伸彦
    • Organizer
      フォーラム2018 衛生薬学・環境トキシコロジー シンポジウム「生殖毒性の最前線」
    • Related Report
      2017 Annual Research Report
  • [Presentation] Titanium dioxide nanoparticle-induced testicular toxicity in mice2017

    • Author(s)
      Miura N and Ohtani K
    • Organizer
      Society of Toxicology
    • Place of Presentation
      Baltimore
    • Year and Date
      2017-03-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Titanium dioxide nanoparticle-induced testicular toxicity in mice2017

    • Author(s)
      Nobuhiko Miura and Katsumi Ohtani
    • Organizer
      The 56th Annual Meeting of Society of Toxicology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酸化チタンナノ粒子による精巣機能障害-肝障害との比較-2017

    • Author(s)
      三浦伸彦,北條理恵子,大谷勝己
    • Organizer
      フォーラム2017衛生薬学・環境トキシコロジー
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸化チタンのマウス雄性生殖系への影響2017

    • Author(s)
      大谷勝己,北條理恵子,三浦伸彦
    • Organizer
      フォーラム2017衛生薬学・環境トキシコロジー
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸化チタンナノ粒子による精巣障害および肝障害の比較2017

    • Author(s)
      三浦伸彦,北條理恵子,吉岡弘毅,大谷勝己
    • Organizer
      生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスにおける酸化チタンの雄性生殖系への影響2017

    • Author(s)
      大谷勝己,北條理恵子,吉岡弘毅,三浦伸彦
    • Organizer
      生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 二酸化チタンの結晶構造と精巣機能障害2016

    • Author(s)
      三浦伸彦
    • Organizer
      メタルバイオサイエンス研究会サテライト
    • Place of Presentation
      静岡県立大学
    • Year and Date
      2016-08-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] Adverse effect of titanium dioxide nanoparticle on testicular function in mice2016

    • Author(s)
      Miura N, Ohtani K
    • Organizer
      Society of Toxicology
    • Place of Presentation
      New Orleans
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 酸化チタンナノ粒子が精巣及び精子に与える影響解析2015

    • Author(s)
      三浦伸彦,大谷勝己
    • Organizer
      フォーラム2015衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] チタンナノ粒子による精巣機能障害の誘発2015

    • Author(s)
      三浦伸彦,大谷勝己
    • Organizer
      メタルバイオサイエンス研究会
    • Place of Presentation
      名古屋国際センター
    • Year and Date
      2015-08-28
    • Related Report
      2015 Annual Research Report
  • [Remarks] Sci Rep誌への掲載分1件を追加登録願います。

    • Related Report
      Products Report

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Published: 2015-04-16   Modified: 2021-07-06  

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